The Therapeutic Potential of Adipose Tissue-Derived Mesenchymal Stem Cells to Enhance Radiotherapy Effects on Hepatocellular Carcinoma

Lingyun Wu; Qiuying Tang; Xin Yin; DanFang Yan; Mengmeng Tang; Jiaojiao Xin; Qiaoling Pan; Chiyuan Ma; Senxiang Yan

doi:10.3389/fcell.2019.00267

The Therapeutic Potential of Adipose Tissue-Derived Mesenchymal Stem Cells to Enhance Radiotherapy Effects on Hepatocellular Carcinoma

Front Cell Dev Biol. 2019 Nov 12:7:267. doi: 10.3389/fcell.2019.00267. eCollection 2019.

Authors

Lingyun Wu¹, Qiuying Tang¹, Xin Yin¹, DanFang Yan¹, Mengmeng Tang², Jiaojiao Xin³, Qiaoling Pan³, Chiyuan Ma⁴, Senxiang Yan¹

Affiliations

¹ Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Orthopaedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Several studies have investigated strategies to improve the clinical efficacy of radiotherapy (RT) against hepatocellular carcinoma (HCC), yet the prognosis remains poor. Human adipose tissue-derived mesenchymal stem cells (AT-MSCs), easily accessible and abundant in quantity, have represented as an attractive therapeutic tool for the stem cell-based treatment for cancer diseases. Through direct co-culture and indirect separate culture experiments, we showed that AT-MSCs could enhance inhibitory effect of RT on reducing HCC cell growth, migration and invasion in both in vitro and in vivo experiments. RNA-sequencing analysis revealed a noticeable interferon-induced transmembrane 1 (IFITM1)-induced tumor gene signature. Gain and loss of mechanistic studies indicated that mechanism was attributed to downregulated expression of signal transducer and activator of transcription 3 (STAT3) and matrix metallopeptidases (MMPs) and upregulated expression of P53 and caspases. Collectively, our findings suggest that AT-MSCs might enhance the therapeutic effects of RT on HCC, providing a rationale for AT-MSCs and RT combination therapy as a new remedy for HCC.

Keywords: adipose tissue-derived mesenchymal stem cells; combination therapy; hepatocellular carcinoma; interferon-induced transmembrane 1; radiotherapy.